tbuckley/cabot-search huggingface dataset:
Clinical and molecular characteristics of advanced esophageal/GEJ cancer with brain metastasis.
Authors: Kai-li Liang, Josephine Louella Feliciano, Kristen Marrone, Joseph Christopher Murray, Sean Tackett, Russell K. Hales, K. Ranh Voong, Richard James Battafarano, Stephen Yang, Stephen Broderick, Jinny Suk Ha, Patrick M. Forde, Julie R. Brahmer, Vincent K. Lam
Journal: Journal of Clinical Oncology (2022)

e16092 Background: Brain metastasis (BRM) in gastroesophageal (GE) cancer is uncommon, but contributes to poor prognosis and significant symptom burden. While HER2 overexpression has been suggested as a potential driver of BRM, clinicopathologic and molecular determinants of BRM in GE cancer and their impact on clinical outcome remain incompletely understood. Methods: We retrospectively analyzed clinicopathologic data from 323 advanced esophageal/GEJ patients (pts) at Johns Hopkins from 2003 to 2021. Univariate and multivariate logistic regression were performed to investigate the association between several clinical and molecular features and the occurrence of BRM, with particular focus on HER2 overexpression (by IHC and FISH) and PD-L1 expression (by IHC) as measured by the combined positive score (CPS). Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 64 and most pts were white (90.4%). Tumors were 73.7% esophageal primary, 82.7% adenocarcinoma, 43.8% HER2+, and 11.1% CPS ≥ 1. Cumulative incidence of BRM in overall cohort and within HER2+ subgroup was 14.6% (47 pts) and 25.4% (16 pts), respectively. Pts with BRM (not already present at time of stage IV diagnosis) had median onset of 10.8 months. Seventeen (36.2%) pts had a solitary brain lesion and 10 (21.7%) were asymptomatic. On univariate analysis, adenocarcinoma and HER2 overexpression were associated with increased risk of BRM (OR 3.45; 95% CI 0.09-0.96; p = 0.043 and OR 2.72; 95% CI 1.11-6.67; p = 0.028, respectively). Notably, the HER2 association was strengthened when HER2 equivocal tumors were re-classified as positive in an exploratory analysis (OR 3.55; 95% CI 1.38-9.14; p = 0.009). Adenocarcinoma and HER2 overexpression were collinear in the multivariate model. In pts with BRM, OS was improved in HER2+ pts (16.72 months; 95% CI 12.3-21.1 months; log-rank p = 0.039 and OR 0.33; 95% CI 0.11-0.99; Cox regression p = 0.049). CPS and primary tumor location were not associated with increased BRM. Conclusions: HER2 overexpression identifies an esophageal/GEJ molecular subtype that is significantly associated with increased risk of BRM; though with improved OS (compared to non-HER2+ BRM) and later onset CNS progression, likely reflecting durable extra-CNS control on targeted systemic therapy and a potential HER2+ subgroup with relatively indolent biology. Prevalence of asymptomatic and solitary brain lesions supports increased brain surveillance for this population.
HGG-62. Molecularly guided treatment of mismatch repair-deficient pediatric brain tumors
Authors: Erin Crotty, Bonnie Cole, Shannon Stasi, Nicholas Vitanza, Vera Paulson, Christina Lockwood, Sarah Leary
Journal: Neuro-Oncology (2022)

Abstract Mismatch repair (MMR)-deficient brain tumors, defined by high tumor mutational burden (TMB) and alterations in MMR or DNA proofreading genes, may harbor therapeutic vulnerabilities to immune checkpoint inhibition (ICI) and resistance to temozolomide. We report a single-institution experience incorporating a personalized genomics approach for pediatric brain tumor patients with high TMB. Tumor and peripheral blood samples were obtained at surgery or autopsy and molecular profiling performed by UWOncoPlex, a multiplexed DNA sequencing panel. Treatment and survival information was obtained by medical records review. Tumor types included high-grade glioma (10, including 1 DIPG), and desmoplastic/nodular medulloblastoma (1). Metachronous tumors were present in three patients and median age at diagnosis was 11.5 years (range 8 – 18). Constitutional predisposition included MMR deficiency (CMMRD), Lynch syndrome, and polymerase proofreading deficiency (PPD). All patients had localized disease, with gross total resection achieved in 6/11 (55%). All received radiation (RT), with concurrent temozolomide delivered in HGG (9). 7/9 patients (78%) with HGG had radiographic progression following RT/temozolomide. Five patients received ICI with pembrolizumab (4), nivolumab/ipilimumab (2), or nivolumab alone (1). Two patients progressed on pembrolizumab then had partial responses to dual nivolumab/ipilimumab. Another patient had a complete response to pembrolizumab and remains disease-free nearly 1 year after discontinuing drug due to reactivated skin GHVD. While not statistically significant in this small cohort, median survival of ICI-treated patients (5) compared to those who received alternative therapies (6) was 40.4 vs. 17.7 months. Patients with durable responses &amp;gt;18 months to ICI (3) included one who underwent surgical debulking following nivolumab, and two patients molecularly classified as CMMRD + somatic PPD. This series highlights the importance of integrating molecular findings and identification of high TMB early in clinical diagnosis and supports the use of ICI to achieve durable responses in children with MMR-deficient brain tumors.
Cytokine as an potential prognostic factor associated with absolute value of neutrophil and serum albumin in breast cancer patients.
Authors: Ye Zhu, Jingyi Zhang, Chong Chen, Zhongsheng Tong, Weipeng Zhao
Journal: Journal of Clinical Oncology (2022)

e13007 Background: Cytokines are involved in many inflammatory diseases through various ways and play an important role in tumor immune regulation. With the development of molecular biology these years, researchers have found that breast cancer is not only related to genetic and environmental factors, but also to the chronic inflammation and immunity. But at the moment，there are few studies on the prognostic evaluation of serum cytokines in breast cancer. The correlation between serum cytokines and leukocytes was not clear. The purpose of this study is to investigate the value of serum cytokines in prognosis of breast tumors and their relationship with leukocyte characters and serum albumin level. Methods: A total of 75 serum samples and clinicopathological data of breast cancer patients from Tianjin Medical University Cancer Institute and Hospital were collected. The expression levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-α, IFN-γ) in serum were detected by immunofluorescence method. The absolute value of different kinds of leukocyte were determined by automatic blood analyzer. The concentration of albumin (ALB) was determined by bromocresol green method (BCG method). Univariate Cox regression and multivariate Cox regression were used to analyze the influence of the above indexes and clinicopathological features on the prognosis of patients. The correlation between the expression of cytokines and the absolute value of various kinds of leukocyte and serum albumin was studied by using multiple regression analysis. Results: A multivariate Cox proportional risk model was established by including breast cancer stage, molecular typing, IL-10, IL-12p70, absolute value of neutrophil, serum albumin and dipeptide aminopeptidase. It showed that different breast cancer stage (HR=0.415, 95%CI 0.191-0.902, P=0.026), and IL-10 (HR=0.177, 95%CI 0.038-0.821, P=0.027) were independent prognostic factors, Luminal B breast cancer had a statistically significant impact on survival compared with triple negative breast cancer (HR=0.193, 95%CI 0.067-0.554, P=0.002). The effect of other variables on survival was not statistically significant (P&gt;0.05). Multiple linear regression analysis model demonstrated that the absolute value of neutrophils (b=1.498, t =2.938, P=0.005) and serum albumin (b=1.253, t=2.777, P=0.007) had statistically significant differences on IL-10, but breast cancer stage (b=0.635, t=1.776, P=0.08) and dipeptide aminopeptidase had no significant difference (b=0.952, t=1.715, P=0.091). Conclusions: Serum IL-10 plays an important role in indicating the prognosis of patients with breast cancer and its expression level was closely correlated with absolute value of neutrophil and serum albumin.
Mainstreamed genetic testing of patients with breast cancer: Experience from a single surgeon’s practice in a large U.S. academic center.
Authors: Kanhua Yin, Teresa S Chai, Mackenzie Wooters, Kristen M Shannon, Kevin S. Hughes
Journal: Journal of Clinical Oncology (2022)

10577 Background: Germline genetic testing for cancer susceptibility has proven to be a powerful tool in cancer risk assessment, screening, and prevention but a huge gap exists between the number of germline genetic testing candidates and the number of patients actually tested. This study aimed to evaluate the impact of mainstreamed genetic testing (MGT) model into a single academic breast surgeon’s practice on genetic test completion. Methods: Before September 2019 (pre-MGT phase), a breast surgery practice at Massachusetts General Hospital followed a traditional model of pre-test consultation with a genetic professional. After September 2019 (post-MGT phase), the same practice offered eligible patients with immediate testing in the same visit. We evaluated the appointment completion in the pre-MGT phase and compared the test uptake and test results between the two phases. Results: We identified 204 patients in the pre-MGT phase and 202 patients in the post-MGT phase. In the pre-MGT phase, the median waiting time for genetic counseling was seven days for patients with a newly diagnosed cancer, 211 days for patients with a remote personal history of cancer, and 224 days for non-cancer patients who had a family history. A total of 105 (51.5%) patients completed a genetic counseling appointment (Table). In the post-MGT phase, a significantly higher proportion of patients (88.1%, p &lt; 0.001) consented to genetic testing, while the proportion of patients who tested positive was lower (pathogenic variant: 11.9% vs. 20.0%; variant of uncertain significance: 19.9% vs. 28.0%; p = 0.047). Conclusions: Implementing MGT can reduce the number of clinical visits, significantly shorten patients’ wait time to test initiation, and increase the completion of genetic testing. [Table: see text]
The impact of pembrolizumab on patients with pre-existing autoimmune diseases.
Authors: Noor Bazerbashi, Ibrahim Muhsen, Ethan Burns, Maen Abdelrahim
Journal: Journal of Clinical Oncology (2022)

2660 Background: Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape across a range of solid and hematologic malignancies. With the mechanistic activation of the adaptive immune response and known unique development of immune-related adverse effects (irAE), there is a theoretical risk of causing detrimental effects on patients with pre-existing autoimmune diseases (AID). However, this patient population was excluded from many clinical trials, and there is limited and conflicting retrospective data speculating upon the impacts of using ICI therapy in patients with AID. This study aims to report the impact of pembrolizumab in patients with AID. Methods: Patients who received pembrolizumab for treatment of any type of cancer between 1/1/2017-8/1/2021 were retrospectively reviewed, and patients with AID (rheumatologic or non-rheumatologic) were identified. Data including age, gender, race, ECOG, and primary cancer diagnosis were collected. AID was characterized by type, activity (symptomatic vs. asymptomatic at ICI initiation), and immunosuppressive treatment (IST) use. Outcomes included flare of AID, irAE, and ICI discontinuation. Results: Out of 810 patients, 12 with pre-existing AID were found and being treated for non-small cell lung cancer (NSCLC) (58% N=7), renal cell carcinoma (RCC) (16.6% N=2), colorectal cancer (CRC) (8% N=1), head and neck cancer (8% N=1), and cervical cancer (8% N=1). Around 67% of these patients were females with a median age of 65 years (50-77). Median ECOG was 1 (0-2). 9 patients (75%) had rheumatologic disease (5 rheumatoid arthritis (RA), 1 systemic lupus erythematosus (SLE), 2 psoriatic arthritis, and 1 systemic sclerosis (SS)). 3 patients (25%) had non-rheumatologic AID (1 multiple sclerosis (MS), 1 autoimmune hepatitis, and 1 Evan’s syndrome). All patients were asymptomatic prior to initiation of therapy. At the time of ICI initiation, 11 patients (92%) were on therapy, including steroids, methotrexate, and other IST. Due to concern for severe flare, pembrolizumab was discontinued in 3 (25%) MS, RA, and SS patients treated for RCC, CRC, and NSCLC, respectively. 3 patients (25%) developed irAE unrelated to their AID (pneumonitis, dermatitis, arthritis, gastritis) and received steroids. 4 patients (33.3%) had documented flares while on pembrolizumab requiring escalation of their ongoing therapy, and 1 NSCLC patient had a severe exacerbation of SS requiring cyclophosphamide and rituximab infusions. Conclusions: This analysis adds to the limited available literature that patients with an AID and on IST appear to have minimal AID-associated flares requiring intervention and tolerate pembrolizumab with a similar rate of irAE compared to patients without AID. Additional larger studies are needed to assess the efficacy of treatment in this population.
The longitudinal impact of COVID-19 on the diagnosis and treatment of lung cancer at a Canadian academic center: Interim analysis from a retrospective chart review.
Authors: Angelo Rizzolo, Goulnar Kasymjanova, Carmela Pepe, Jennifer Elisabeth Friedmann, David I. Small, Colton Price-Gallagher, Jonathan Spicer, Christian Sirois, Magali Lecavalier-Barsoum, Khalil Sultanem, Hangjun Wang, Alan Spatz, Victor Cohen, Jason S. Agulnik
Journal: Journal of Clinical Oncology (2022)

e18737 Background: The coronavirus disease 2019 (COVID-19) has significantly impacted clinical activities across many medical specialties. The care of lung cancer (LC) patients is no exception. Our group recently reported that the rate of new lung cancer diagnoses declined by 35% during the first year of COVID-19 pandemic (year 2020). The objective of the present study is to continue to evaluate changes in lung cancer diagnosis and management during 3 rd and 4 th waves of the pandemic (2021). Methods: This is a retrospective chart review study including patients diagnosed with lung cancer between March 1 st 2019 and February 1 st 2022 at the Jewish General Hospital, Montreal, QC, Canada. We compared 3 cohorts: Cohort 1: 2019 (pre-COVID). Cohort 2: 2020 (1 st year of COVID). Cohort 3: 2021 (2 nd year of COVID; reporting for 10 months of 2021). Results: A total of 388 patients were diagnosed with lung cancer throughout the three-year study: 130 in cohort 1, 103 in cohort 2 and 155 in cohort 3. Although there was a 35% decline of new lung cancer (LC) diagnoses observed in the 1 st year of COVID, there was a 50% increase in diagnoses during the 2 nd year comparing to the first year and a 19.2% increase compared to the pre-COVID year. Stage 4 LC diagnoses increased by 29% in 2021 compared to 2019 (88 cases vs 68 cases) and by 54% compared to 2020 (88 cases vs 57 cases). Early stage curative treatments (which had significantly changed in 2020, as the use of radiation therapy [RT] increased by 125% and surgery decreased by 38%), approached pre-pandemic levels in 2021. In 2021 we observed a decrease in RT and a significant increase in surgical resections. Analyses of wait time for initiation of treatment is still ongoing. Conclusions: The present study represents interim data in our ongoing effort to evaluate the dynamic impacts of the COVID-19 pandemic on diagnosis and delivery of LC care. The pattern of lung cancer treatment modalities for early stage disease appears to be recovering to pre-COVID rates. However, the significant decrease in lung cancer diagnoses during the first year of the pandemic has resulted in an increase in new diagnoses during the 2 nd year at unfortunately more advanced stage of disease.[Table: see text]
Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial
Authors: Bruce E Sands, Peter M Irving, Timothy Hoops, James L Izanec, Long-Long Gao, Christopher Gasink, Andrew Greenspan, Matthieu Allez, Silvio Danese, Stephen B Hanauer, Vipul Jairath, Tanja Kuehbacher, James D Lewis, Edward V Loftus, Emese Mihaly, Remo Panaccione, Ellen Scherl, Oksana B Shchukina, William J Sandborn, Anita Afzali, Lilia Aitova, Xavier Aldeguer i Mante, Matthieu Allez, István Altorjay, Federico Argüelles Arias, Alessandro Armuzzi, Monika Augustyn, Mauro Bafutto, Jesus Barrio, Jakob Begun, Clint Behrend, Geert Bezemer, Guillaume Bonnaud, Marija Brankovic, Ik Jang Byung, Xavier Calvet Calvo, Karen Chachu, Julio Maria Fonseca Chebli, Jae Hee Cheon, Halina Cichoz-Lach, Larry Clark, Fraser Cummings, Kunal Dalal, Silvio Danese, Nanne De Boer, Maria De Lourdes Ferrari, Etienne Désilets, Predrag Dugalic, George Duvall, Olga Fedorishina, Rafal Filip, Cristina Flores, Ronald Fogel, James Fon, Michael Frankel, Keith Friedenberg, Walter Fries, Vassileva Galina, Piotr Gietka, Rishi Goel, Peter Hasselblatt, Hans Herfarth, László Herszényi, Pieter Hindryckx, Frank Hoentjen, Carmen Horjus Talabur Horje, Satish Iduru, Peter Irving, Robert Isfort, Vipul Jairath, Michael Jones, Dilara Kalimullina, Jeffry Katz, Manreet Kaur, Sunil K Khurana, Joo Sung Kim, Youngho Kim, Dariusz Kleczkowski, Slavko Knezevic, Aaron Knoll, Louis Y Korman, Iskren Kotzev, Andrey Kulyapin, Kang Moon Lee, Desiree Leemreis, Jaroslaw Leszczyszyn, Jimmy Limdi, Jack Lissauer, Edward Loftus, Ewa Malecka-Panas, John Marshall, Emese Mihály, Lukas Milan, Giovanni Monteleone, Aleksandar Nagorni, Danuta Owczarek, Nichole Palekar, Remo Panaccione, Young Soo Park, Sang Hyoung Park, Rogério Parra, Árpád Patai, Kamal Patel, Bhaktasharan Patel, Anatoly Pershko, Elina Petrova, Guillaume Pineton de Chambrun, Charles Randall, Sabino Riestra Menendez, Timothy Ritter, Montserrat Rivero, Xavier Roblin, Rodolfo Rocca, Jacek Romatowski, Grazyna Rydzewska, Simone Saibeni, Bruce Salzberg, Harry Sarles, John Saunders, Edoardo Vincenzo Savarino, Zuzana Serclova, Oksana Shchukina, Jonathan Siegel, Najm Soofi, Miles Sparrow, David Stokesberry, Daniel Suiter, Petar Svorcan, Alexander Tkachev, Nikolay Tsonev, Kristóf Tünde, Jan Ulbrych, Tomas Vanasek, Márta Varga, Severine Vermeire, Raquel Vicente Lidon, Michael L Weiss, Emma Wesley, Nathaniel Winstead, Katarzyna Wojcik, Joanna Wypych, Cyrla Zaltman, Zadorova Zdena
Journal: The Lancet (2022)
Magnetic double-J vs. traditional double-J stent: Evaluation of tolerance and impact on quality of life
Authors: M. Diranzo Garcia, P. Pardo Duarte, A. Álvarez Barrera, M. Beltrán Puig, K. Rechi Sierra, F. Martinez Martinez, R. Gras Martínez, S. Mitjana Biosca, J. Garcia Ibáñez, E. López Alcina
Journal: European Urology (2022)
Selective inhibition of METTL3 enhanced anticancer activity via targeting the c-Myc pathway.
Authors: Paramasivam Arumugam, Vijayashree Priyadharsini Jayaseelan
Journal: Journal of Clinical Oncology (2022)

e15089 Background: Methyltransferase-like 3 (METTL3) is a master regulator enzyme in the N6-methyladenosine (m6A) methyltransferase system, that not only plays a crucial role in cancer but has become a promising therapeutic target for the same. This study was aimed to discover molecular mechanisms underlying the potential anticancer effects of a novel and selective METTL3 inhibitor named STM2457 against oral squamous cell carcinoma (OSCC). Methods: OSCC patient-derived organoids (PDOs) and the corresponding 2D cell lines were established from the patients who have increased expression of METTL3 and c-Myc. The pharmacological activity of STM2457 was extensively studied with organoids and primary OSCC cells. Cell proliferation, wound healing and colony formation assays were used to detect STM2457 anticancer activity in vitro. Patient-Derived tumor Xenograft (PDX) model of OSCC was used to detect STM2457 anticancer activity in vivo. m6A level of mRNA was measured by an m6A-RNA methylation quantification kit. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to screen the target genes of METTL3. RNA stability assay was used to detect the half-lives of METTL3 target genes. Real-time quantitative PCR was used for gene expression and western blot was used for protein expression analysis. Results: We found that STM2457 treatment exerted potential anticancer activity in PDOs and primary OSCC cells. MeRIP-seq revealed that c-Myc was the downstream gene of METTL3. Functionally, knockdown or pharmacological inhibition of METTL3 by STM2457 reduced stability and expression of c-Myc. This eventually, results in significant attenuation of migration, invasion, tumorsphere formation, and colony formation abilities of OSCC cells. Moreover, STM2457-treated OSCC cells showed reduced tumorigenic activity in vivo. Furthermore, STM2457 treatment reduced m6A level in PDOs and OSCC cells by blocking METTL3 activity thereby elucidating the importance of personalized approach for effective cancer treatment. Conclusions: Altogether, the revelation of anticancer effect of STM2457 exerted by blocking of METTL3-c-Myc signaling pathway opens novel avenues into the field of epitranscriptomics.
Addressing unmet needs of cancer care in a lower middle income country by establishing an electronic hospital based cancer registry.
Authors: Sanjeeva Gunasekera, Sanjeewa Seneviratne, Hasitha Pramod, Laura M. Carson, Scott Berry, Christopher M. Booth, Thiwanka Wijeratne
Journal: Journal of Clinical Oncology (2022)

e13621 Background: Sri Lanka (SL) is a Lower Middle Income Country (LMIC) which has seen its cancer incidence double in the last 25 years. National Cancer Institute Sri Lanka (NCISL) is the only dedicated cancer hospital in SL and provide care to around 40% of all patients diagnosed with cancer in the country. The existing SL Cancer Registry, primarily contains only socio-demographic data and there was no systematic method to capture cancer treatment and outcome data This presents a missed opportunity in identifying and bridging gaps in cancer care delivery and health equities in an effective manner. Methods: We built an electronic hospital based cancer registry using the “free to use” cloud based District Health Information System (DHIS2) software platform and prospectively collected disease, demographic, treatment and outcome data on selected cancers treated at the NCISL from 2016 onwards. This platform is easily adaptable and will allow downloading data to standard statistical software directly for data analysis and can be integrated with other existing health information systems. its easily adaptable . The variables captured were identified through focus group sessions with both healthcare workers and patient representatives. Results: To date, data from over 5,000 breast, 1500 colorectal and 600 thyroid cancer patients have been captured. From this database data on disease characteristics, demographic details, survival rates, treatment toxicities, referral pathways, health care seeking patterns, comorbidity data, health care related quality of life, treatment guideline concordance, out of pocket expenses incurred while on treatment, palliative care delivery, cancer care equity gaps can be elicited. Conclusions: Our database demonstrates that it is feasible to build low cost, easy to maintain yet good quality custom made data bases to collect cancer care related data. Careful selection of variables will allow health systems to identify existing gaps which is the key initial step in addressing them with a view of improving cancer related outcomes. Integrating demographic and outcome data within the same database will help in identifying health system inequities. Continuous data collection will allow assessing the efficacy of any intervention launched to bridge these gaps in the future. This database can also be adapted with minimal change by other LMICs to generate real world data to inform national cancer control policy planning.